PB1731: INOTUZUMAB OZOGAMICIN IN LYMPHOID B-CELL MALIGNANCY：A SINGLE CENTER ANALYSIS IN THE REAL WORLD
Authors: Mengnan LV, Yi He, Donglin Yang, Qiaoling MA, Aiming Pang, Weihua Zhai, Jialin Wei, Yong Huang, Xin Chen, Guixin Zhang, Sizhou Feng, Mingzhe Han, Rongli Zhang, Erlie Jiang
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Recent developments in immunoconjugate usage has changed the landscape of lymphoid B-cell malignancy therapy. Historically, those who relapse from this condition have a dismal prognosis and limited treatment options. One recent development is the inotuzumab ozogamicin (INO), a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, which has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to show therapeutic effects in relapsed/refractory lymphoid B-cell malignancy. Aims: The activity and safety of INO was evaluated in patients with lymphoid B-cell malignancy in our center. Methods: The study included B cell-acute lymphoblastic leukemia (B-ALL) (Ph+/-) (n=17), B/ myeloid mixed phenotype acute leukemia (MPAL) (n=1) and B-cell lymphoblastic lymphoma (B-LBL) (n=2) adult patients who received INO in our center from June 2022 to Jan 2023. Intravenous INO was given 1 or more doses at the dose of 0.6mg/m2, its clinical efficacy and adverse reactions were explored. Results: In our center, INO was attempted to be administered in induction (n=2), maintenance/consolidation (n=6), MRD clearance (n=3) and relapsed/refractory lymphoid B-cell malignancy treatment (n=9). 9 out of 20 patients were treated with INO combined with chemotherapy for recurrence and refractory lymphoid B-cell malignancy, of which 2 patients relapsed after regular chemotherapy, 1 patient relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), 4 patients relapsed after autologous hematopoietic stem cell transplantation (auto-HSCT) (All were B-ALL patients with bone marrow morphological recurrence) and the other 2 were refractory cases (1 in B-ALL and 1 in B-LBL). The medium dose was 2 (1-3) doses. A complete remission (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 7/9 (77.8%) patients at the medium time of 30 days; 1/9 (11.1%) patients achieved partial response (PR) and the overall response rate (ORR) was 88.9%. Negative measurable residual disease (MRD) was noted in 6/9 (66.7%) patients. 2 (28.6%) patients relapsed again 2 and 2.5 months after achieving CR/Cri but no patient died. For MRD clearance, it was successfully removed in 3 (100%) patients (2 in B-ALL and 1 in B-LBL/ALL) treated with INO at the medium time of 44 days and 2 of them received HSCT afterwards. The mortality and recurrence rate were 0%. In addition, the induction regimen administered was VICLP combined with INO in 2 (100%) patients and MRD turned negative after the treatment. As for the remaining 6 patients, INO was given to 3 patients (2 in B-ALL and 1 in MPAL) with high-risk factors or intention to underwent auto-HSCT as consolidation treatment. Another 3 B-ALL patients treated with INO as maintenance therapy after auto-HSCT or after the remission of recurrence after transplantation. All these 6 patients had achieved negative MRD before INO and maintained till now. No patient died or stopped medication from adverse events that were deemed treatment related. 15/20 (75%) had grade 3-4 hematological toxicity, 1/20 (5%) had grade 3 ALT elevation and no patient had veno-occlusive disease (VOD). 2 patients developed Escherichia coli and Klebsiella pneumoniae septicemia respectively Summary/Conclusion: Given the well tolerance and substantial improvement in response rates, InO may be an important treatment option not only for patients with relapsed/refractory lymphoid B-cell malignancy, but also for induction, maintenance and MRD clearance treatment.Keywords: Minimal residual disease (MRD), ALL, Relapse, Refractory